Optogenetic Tools for Minimally Invasive Therapies

用于微创治疗的光遗传学工具

• 批准号: 1264975
• 负责人: Brian Chow
• 金额: $ 42.55万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1264975&HistoricalAwards=false
• 关键词: Optogenetic; Tools; Minimally; Invasive; Therapies

1264975ChowThe ability to rationally convert a microbial opsin pump into a channel would validate a fundamental hypothesis in ion channel structure-function, which states that a key difference between a pump and a channel is the existence of a gate that prevents backflow of ions by passive conductance and enables active ion translocation against large gradients. This biophysical feat of rational conversion by protein engineering would be the first of its kind. Furthermore, while the activity-dependent safety of neural silencing by proton and chloride pumps has been evaluated in the literature, the creation of optogenetic reagents specifically for the purpose of activity-dependent safety is novel. Moreover, the translationally focused goal of engineering a calcium-free channelrhodopsin to reduce risk of excito-toxicity is in fact opposite to ongoing efforts in the field, which seek to augment calciumconductance to increase sensitivity. The creation of reagents, whose molecular properties are tailored for translational purposes, would represent a new direction in optogenetic reagent development, which to date have focused on pushing the limits of microbial opsin photocurrent magnitude, kinetics, and spectral properties.

1264975授予理性转换微生物蛋白泵为通道的能力将验证离子通道结构功能中的基本假设，该假设指出，泵和通道之间的关键差异是存在被动电导的栅极，并且可以通过被动电导率进行回流，并可以抵抗大型梯度的主动离子转移。蛋白质工程的这种合理转化的生物物理壮举将是同类的。此外，尽管在文献中评估了质子和氯化物泵的神经沉默的活性依赖性安全性，但专门为活动依赖性安全目的而创建了光遗传试剂的创建是新颖的。此外，工程为降低无钙的通道旋转的重点目的是降低抗激素的风险，实际上与该领域的持续努力相反，该田间旨在增加钙的钙传导性以提高敏感性。为了翻译目的而定制的分子特性的试剂的创建将代表光遗传试剂发育的新方向，迄今为止，该方向的重点是推动微生物Opsin光电流幅度，动力学和光谱特性的极限。